麻豆传媒

In the early days of the pandemic, organ donation and transplantation screeched to a halt. Hospitals were at full capacity with an onslaught of COVID-19 patients. Concerns ran high about exposing vulnerable patients to the virus through the organs they'd receive or during inpatient stays.

But transplants in the second half of last year. The move marked a promising sign for organ procurement organizations that work to connect as many donors as possible to the tens of thousands of patients whose life depends on them, as well as for the transplant teams that perform the procedures.

The hope is that a rare fatality doesn't thwart the trend.

Last fall, a Michigan woman a pair of lungs from a donor not immediately known to be infected with COVID-19, Kaiser Health News and other media outlets reported.

The transplant was performed at Michigan Medicine, the health system of the University of Michigan. Officials there said the fatality appears to be the first proven case of COVID-19 in the U.S. that was transmitted through an organ transplant.

Though the case is an anomaly in some 40,000 transplants last year, it has important ramifications for the field. It has spurred interest from organ procurement organizations, the medical community, and the public, and it could lead to stricter guidelines or requirements.

Regardless, experts are keen to keep confidence in transplants on track. With more than 107,000 people waiting for transplants in the U.S., there was already a shortage in organs before the pandemic.

"It should raise our alarm that this can happen and we need to work towards more testing," Daniel Kaul, MD, director of Michigan Medicine's transplant infectious disease service, told 麻豆传媒. "I certainly don't think this case should reduce the number of lung transplants done."

Standard Procedure

In the Michigan case, the donor -- who suffered a severe head injury in a car accident and progressed to brain death within days of being hospitalized -- had no clinical history or radiological evidence suggestive of COVID-19, Kaul and other Michigan Medicine physicians noted in a study . A PCR test on a nasopharyngeal swab obtained within 48 hours of procurement also came back negative.

Lower respiratory tract testing, however, was not performed.

The recipient's condition began deteriorating rapidly within several days of the transplant, and she was placed on a ventilator, according to the study. A bronchoscopy was performed and bronchoalveolar lavage samples were collected from the transplanted lungs. The samples were positive for COVID-19, as was that from a subsequent nasopharyngeal swab.

Suspicion turned to the donor lungs, the physicians wrote. A sample from the lungs retained prior to their transplantation was tested for COVID-19, yielding positive results.

Epidemiological testing revealed the recipient contracted COVID-19 from the donor lungs as did a surgeon who handled them, the physicians wrote. The surgeon recovered, but the recipient's condition continued to decline in the intensive care unit, and she ultimately died two months after the transplant.

This is a case where the screening that was done on the upper airways of the donor was negative and did not uncover infection deep in the lungs that caused transmission of COVID-19 to the recipient, David Klassen, MD, chief medical officer of the United Network for Organ Sharing, told 麻豆传媒. UNOS is the nonprofit that serves as the nation's transplant system -- the Organ Procurement and Transplantation Network -- under contract with the federal government.

Upper respiratory tract testing for COVID-19 in all lung donors has been in place since April of last year, Klassen noted. However, lower respiratory tract testing is currently being done in about one-third of lung donors.

In the Michigan case, lower respiratory tract testing would have identified COVID-19 in the donor.

The OPTN's advisory committee recently related to COVID-19 and transplantation, Klassen noted. The committee reviews data on cases to assess the risk of donor disease transmission in organ transplantation. In turn, it provides education and guidance to the transplant community and input in developing policy to improve the safety of organ donation.

The committee's current recommendation is to use lower respiratory tract testing for COVID-19, especially in lung donors, Klassen noted.

However, he said, the capability isn't currently available in all donor hospitals. UNOS is working to assess how available it is and how to optimally utilize it.

"We're looking at it very carefully, and continuing to monitor it carefully," Klassen said. "At this point, there has been no decision to mandate this kind of testing policy."

"There is always a trade-off, there is always a little bit of risk involved in transplantation," he added. "Hospitals and doctors and recipients have to assess the risk versus the benefit. Turning down an organ offer for someone who is critically ill has some significant consequences."

Additionally, the screening is "robust" and events like the case in Michigan are very rare, Klassen said. "But the approaches are evolving as we learn more about COVID-19. It's not a static situation. We continue to look at all aspects of screening to try to optimize it."

There is hesitation to put a policy in place that could result in a "dramatic decline in the ability to procure lungs for transplants," he said.

Kaul said he believes there needs to be more intensive COVID-19 testing of lung donors whenever possible, including testing of lower respiratory tract samples. He said his colleagues feel the same, as was referenced in the study they co-authored.

"This was an asymptomatic donor," Kaul said. "You do worry about that potentially happening again."

"While the rate of COVID-19 remains high, I do think that working toward more universal testing is worthwhile," he added.

However, there remain challenges to doing so.

Testing Barriers

There has been wide interest in the Michigan case, and it has led to a lot of discussion in the field, Kaul said.

"I don't think it's a simple problem," Kaul said. "The barriers that exist are real nationwide."

In addition to some hospitals or laboratories not having the capability, there may also be concern about not being able to get results back in a short period of time.

Though Scott Spielman, communications manager for the organ procurement organization Gift of Life Michigan, told 麻豆传媒 in an email that the organization could not comment on the specifics of the Michigan Medicine case because it originated with an out-of-state donor and the organization did not facilitate the case, he said that it is always looking at ways to improve testing.

Bruce Nicely, chief clinical officer at Gift of Life Michigan, noted the existence of testing barriers in a statement provided to 麻豆传媒.

"Because of the serious concerns for spreading COVID-19 earlier in the pandemic, many labs refused to run samples from the lower lungs," Nicely said. "However, Gift of Life Michigan has identified a laboratory partner willing and able to test [bronchoalveolar lavage] specimens through a closed system that prevents the spread of droplets or aerosolization. We are finalizing a protocol that has been in development for several weeks to ensure we can collect and test them safely."

Nicely said that "while no lab test is 100% reliable, this procedure, along with regular nasopharyngeal swab testing and our thorough screening of every donor's medical history and current condition, gives us confidence that we are doing everything possible to accurately present a complete picture of the organs being offered for transplantation."

Incredibly Rare

Overall, Kaul of Michigan Medicine said, "We're really more concerned about the donor with asymptomatic COVID-19."

"The risk is probably limited to the lungs," he added. "Although we don't know that for sure."

Research on organ donation and transplantation during the pandemic is ongoing.

A small but promising study of 13 hearts, livers, and kidneys recovered and transplanted through organ procurement organizations in Indiana, New York, and Wisconsin with the organs despite coming from donors who had previously recovered from COVID-19 but then passed away from other causes.

Kaul and his colleagues highlighted the anomaly of the Michigan case in their study, writing that transmission of infection from donor to recipient is uncommon, occurring in less than 1% of cases. However, they added, donor-derived disease is associated with poor outcomes, including death in about one-third of affected recipients.

"Emerging pathogens create particular challenges to assessment of disease transmission risk and recent infectious agents of concern have included H1N1 pandemic influenza, West Nile virus, Ebola virus, and Zika virus," the physicians wrote.

Kaul told 麻豆传媒 that even though transplant recipients are vulnerable to such infections -- in part due to regimens of immunosuppressants they're on to prevent the body from rejecting transplanted organs -- the likelihood of donor-derived disease is incredibly rare.

"I think it's really important that people with organ failure -- including those who need lung transplants -- are not afraid of getting a transplant for this reason," Kaul said. "The risks of declining a transplant are likely to be much more detrimental to health."

Klassen of UNOS concurred.

"I think the fact that we picked up on this case highlights the infrastructure that was preexisting to identify quickly these kinds of cases," Klassen said. "The concept of disease transmission is not new..."

"This is something that we are concerned about," he said, adding, "we're watching for it very closely, and the system responds to these kinds of events to change."

Overall, the safety and number of transplants performed last year -- despite the pandemic -- were "remarkable," he said.

"The goal is to maximize safety," Klassen said, "and at the same time preserve opportunities for transplants for patients who really desperately do need them."

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